Trained Immunity in Childhood Vaccination

ABSTRACT Conventionally, vaccine design has focused on identifying antigens that induce durable T and B cell memory and provide long term protection against subsequent encounters with the same pathogen. Unconventionally, a growing number of epidemiological, preclinical, and clinical studies demonstrate that live vaccines, including Bacillus Calmette Guérin (BCG), measles‐containing vaccines, and oral polio vaccine, induce protection through trained immunity, a form of metabolically and epigenetically mediated memory in innate immune cells and their progenitors. This concept is particularly relevant during early life, when adaptive immune responses are constrained and innate immunity represents the principal line of host defence. In this review, we discuss the unique characteristics of neonatal and infant immunity, summarize current evidence for trained immunity induced by childhood vaccines, and describe the bidirectional interplay between innate and adaptive immune memory. We further highlight the potential of trained immunity to broaden protection against severe infections, improve vaccine efficacy, and provide therapeutic opportunities for non‐infectious paediatric diseases, including cancer and allergic disorders. Harnessing trained immunity represents a conceptual shift in paediatric vaccinology and may guide the development of next generation vaccines that provide broader and more resilient protection during the period of greatest immunological vulnerability.